tbuckley/cabot-search huggingface dataset:
Sbk2, a Newly Discovered Atrium-Enriched Regulator of Sarcomere Integrity
Authors: Pim R.R. van Gorp, Juan Zhang, Jia Liu, Roula Tsonaka, Hailiang Mei, Sven O. Dekker, Cindy I. Bart, Tim De Coster, Harm Post, Albert J.R. Heck, Martin J. Schalij, Douwe E. Atsma, Daniël A. Pijnappels, Antoine A.F. de Vries
Journal: Circulation Research (2022)

Heart development relies on tight spatiotemporal control of cardiac gene expression. Genes involved in this intricate process have been identified using animals and pluripotent stem cell-based models of cardio(myo)genesis. Recently, the repertoire of cardiomyocyte differentiation models has been expanded with iAM-1, a monoclonal line of conditionally immortalized neonatal rat atrial myocytes (NRAMs), which allows toggling between proliferative and differentiated (ie, excitable and contractile) phenotypes in a synchronized and homogenous manner.In this study, the unique properties of conditionally immortalized NRAMs (iAMs) were exploited to identify and characterize (lowly expressed) genes with an as-of-yet uncharacterized role in cardiomyocyte differentiation.Transcriptome analysis of iAM-1 cells at different stages during one cycle of differentiation and subsequent dedifferentiation identified ≈13 000 transcripts, of which the dynamic changes in expression upon cardiomyogenic differentiation mostly opposed those during dedifferentiation. Among the genes whose expression increased during differentiation and decreased during dedifferentiation were many with known (lineage-specific) functions in cardiac muscle formation. Filtering for cardiac-enriched low-abundance transcripts, identified multiple genes with an uncharacterized role during cardio(myo)genesis including Sbk2 (SH3 domain binding kinase family member 2). Sbk2 encodes an evolutionarily conserved putative serine/threonine protein kinase, whose expression is strongly up- and downregulated during iAM-1 cell differentiation and dedifferentiation, respectively. In neonatal and adult rats, the protein is muscle-specific, highly atrium-enriched, and localized around the A-band of cardiac sarcomeres. Knockdown of Sbk2 expression caused loss of sarcomeric organization in NRAMs, iAMs and their human counterparts, consistent with a decrease in sarcomeric gene expression as evinced by transcriptome and proteome analyses. Interestingly, co-immunoprecipitation using Sbk2 as bait identified possible interaction partners with diverse cellular functions (translation, intracellular trafficking, cytoskeletal organization, chromatin modification, sarcomere formation).iAM-1 cells are a relevant and suitable model to identify (lowly expressed) genes with a hitherto unidentified role in cardiomyocyte differentiation as exemplified by Sbk2: a regulator of atrial sarcomerogenesis.
Using open data and open-source software to develop spatial indicators of urban design and transport features for achieving healthy and sustainable cities
Authors: Geoff Boeing, Carl Higgs, Shiqin Liu, Billie Giles-Corti, James F Sallis, Ester Cerin, Melanie Lowe, Deepti Adlakha, Erica Hinckson, Anne Vernez Moudon, Deborah Salvo, Marc A Adams, Ligia V Barrozo, Tamara Bozovic, Xavier Delclòs-Alió, Jan Dygrýn, Sara Ferguson, Klaus Gebel, Thanh Phuong Ho, Poh-Chin Lai, Joan C Martori, Kornsupha Nitvimol, Ana Queralt, Jennifer D Roberts, Garba H Sambo, Jasper Schipperijn, David Vale, Nico Van de Weghe, Guillem Vich, Jonathan Arundel
Journal: The Lancet Global Health (2022)

Benchmarking and monitoring urban design and transport features is critical to achieving local and international health and sustainability goals. However, most urban indicator frameworks use coarse spatial scales that only allow between-city comparisons or require expensive, technical, local spatial analyses for within-city comparisons. This study developed a reusable open-source urban indicator computational framework using open data to enable consistent local and global comparative analyses. We demonstrate this framework by calculating spatial indicators - for 25 diverse cities in 19 countries - of urban design and transport features that support health and sustainability. We link these indicators to cities' policy contexts and identify populations living above and below critical thresholds for physical activity through walking. Efforts to broaden participation in crowdsourcing data and to calculate globally consistent indicators are essential for planning evidence-informed urban interventions, monitoring policy impacts, and learning lessons from peer cities to achieve health, equity, and sustainability goals.
Factors Associated with Use of HIV Prevention and Health Care Among Transgender Women — Seven Urban Areas, 2019–2020
Authors: Kathryn Lee, Lindsay Trujillo, Evelyn Olansky, Taylor Robbins, Christine Agnew Brune, Elana Morris, Teresa Finlayson, Dafna Kanny, Cyprian Wejnert, Narquis Barak, Kathleen A. Brady, Sarah Braunstein, Jasmine Davis, Sara Glick, Andrea Harrington, Jasmine Lopez, Yingbo Ma, Aleks Martin, Genetha Mustaafaa, Tanner Nassau, Gia Olaes, Jennifer Reuer, Alexis Rivera, William T. Robinson, Ekow Kwa Sey, Sofia Sicro, Brittany Taylor, Dillon Trujillo, Erin Wilson, Pascale Wortley
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Transgender women* are disproportionately affected by HIV. Among 1,608 transgender women who participated in CDC's National HIV Behavioral Surveillance (NHBS) during 2019-2020, 42% received a positive HIV test result (1). This report provides results from seven U.S. urban areas where the 2019-2020 NHBS questionnaire was administered. Thirty-eight percent of participants reported having previously received a positive test result for HIV. Detrimental socioeconomic factors, including low income (44%), homelessness (39%), and severe food insecurity in the past 12 months (40%), were common and associated with lower receipt of HIV prevention and treatment services. Having a usual health care source or a provider with whom the participant was comfortable discussing gender-related health issues was associated with improved HIV prevention and treatment outcomes, including HIV testing, preexposure prophylaxis (PrEP) use, and viral suppression. These findings illustrate the benefit of gender-affirming approaches used by health care providers (2), and highlight the challenging socioeconomic conditions faced by many transgender women. Ensuring access to gender-affirming health care approaches and addressing the socioeconomic challenges of many transgender women could improve access to and use of HIV prevention and care in this population and will help achieve the goals of the Ending the HIV Epidemic in the United States initiative (3).
Interleukin-4 receptor signaling modulates neuronal network activity
Authors: Nicholas Hanuscheck, Carine Thalman, Micaela Domingues, Samantha Schmaul, Muthuraman Muthuraman, Florian Hetsch, Manuela Ecker, Heiko Endle, Mohammadsaleh Oshaghi, Gianvito Martino, Tanja Kuhlmann, Katarzyna Bozek, Tim van Beers, Stefan Bittner, Jakob von Engelhardt, Johannes Vogt, Christina Francisca Vogelaar, Frauke Zipp
Journal: The Journal of Experimental Medicine (2022)

Evidence is emerging that immune responses not only play a part in the central nervous system (CNS) in diseases but may also be relevant for healthy conditions. We discovered a major role for the interleukin-4 (IL-4)/IL-4 receptor alpha (IL-4Rα) signaling pathway in synaptic processes, as indicated by transcriptome analysis in IL-4Rα–deficient mice and human neurons with/without IL-4 treatment. Moreover, IL-4Rα is expressed presynaptically, and locally available IL-4 regulates synaptic transmission. We found reduced synaptic vesicle pools, altered postsynaptic currents, and a higher excitatory drive in cortical networks of IL-4Rα–deficient neurons. Acute effects of IL-4 treatment on postsynaptic currents in wild-type neurons were mediated via PKCγ signaling release and led to increased inhibitory activity supporting the findings in IL-4Rα–deficient neurons. In fact, the deficiency of IL-4Rα resulted in increased network activity in vivo, accompanied by altered exploration and anxiety-related learning behavior; general learning and memory was unchanged. In conclusion, neuronal IL-4Rα and its presynaptic prevalence appear relevant for maintaining homeostasis of CNS synaptic function.
Clinical significance of plasma-free amino acids and tryptophan metabolites in patients with non-small cell lung cancer receiving PD-1 inhibitor: a pilot cohort study for developing a prognostic multivariate model
Authors: Koichi Azuma, Huihui Xiang, Tomoyuki Tagami, Rika Kasajima, Yumiko Kato, Sachise Karakawa, Shinya Kikuchi, Akira Imaizumi, Norikazu Matsuo, Hidenobu Ishii, Takaaki Tokito, Akihiko Kawahara, Kenta Murotani, Tetsuro Sasada, Yohei Miyagi, Tomoaki Hoshino
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Amino acid metabolism is essential for tumor cell proliferation and regulation of immune cell function. However, the clinical significance of free amino acids (plasma-free amino acids (PFAAs)) and tryptophan-related metabolites in plasma has not been fully understood in patients with non-small cell lung cancer (NSCLC) who receive immune checkpoint inhibitors. Methods We conducted a single cohort observational study. Peripheral blood samples were collected from 53 patients with NSCLC before treatment with PD-1 (Programmed cell death-1) inhibitors. The plasma concentrations of 21 PFAAs, 14 metabolites, and neopterin were measured by liquid chromatography–mass spectrometry. Using Cox hazard analysis with these variables, a multivariate model was established to stratify patient overall survival (OS). Gene expression in peripheral blood mononuclear cells (PBMCs) was compared between the high-risk and low-risk patients by this multivariate model. Results On Cox proportional hazard analysis, higher concentrations of seven PFAAs (glycine, histidine, threonine, alanine, citrulline, arginine, and tryptophan) as well as lower concentrations of three metabolites (3h-kynurenine, anthranilic acid, and quinolinic acid) and neopterin in plasma were significantly correlated with better OS (p&lt;0.05). In particular, the multivariate model, composed of a combination of serine, glycine, arginine, and quinolinic acid, could most efficiently stratify patient OS (concordance index=0.775, HR=3.23, 95% CI 2.04 to 5.26). From the transcriptome analysis in PBMCs, this multivariate model was significantly correlated with the gene signatures related to immune responses, such as CD8 T-cell activation/proliferation and proinflammatory immune responses, and 12 amino acid-related genes were differentially expressed between the high-risk and low-risk groups. Conclusions The multivariate model with PFAAs and metabolites in plasma might be useful for stratifying patients who will benefit from PD-1 inhibitors.
Comparative transcriptomics reveals circadian and pluripotency networks as two pillars of longevity regulation
Authors: J. Yuyang Lu, Matthew Simon, Yang Zhao, Julia Ablaeva, Nancy Corson, Yongwook Choi, KayLene Y.H. Yamada, Nicholas J. Schork, Wendy R. Hood, Geoffrey E. Hill, Richard A. Miller, Andrei Seluanov, Vera Gorbunova
Journal: Cell Metabolism (2022)
Single-cell analysis identifies the interaction of altered renal tubules with basophils orchestrating kidney fibrosis
Authors: Tomohito Doke, Amin Abedini, Daniel L. Aldridge, Ya-Wen Yang, Jihwan Park, Christina M. Hernandez, Michael S. Balzer, Rojesh Shrestra, Gaia Coppock, Juan M. Inclan Rico, Seung Yub Han, Junhyong Kim, Sheng Xin, Adrian M. Piliponsky, Marco Angelozzi, Veronique Lefebvre, Mark C. Siracusa, Christopher A. Hunter, Katalin Susztak
Journal: Nature Immunology (2022)
Risk-adapted chemoimmunotherapy using brentuximab vedotin and rituximab in children, adolescents, and young adults with newly diagnosed Hodgkin’s lymphoma: a phase II, non-randomized controlled trial
Authors: Jessica Hochberg, Jaclyn Basso, Qiuhu Shi, Liana Klejmont, Allyson Flower, Kristina Bortfeld, Lauren Harrison, Carmella van de Ven, Chitti Moorthy, Humayun Islam, Perry Gerard, Stephan Voss, Mitchell S Cairo
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Cure rates for Hodgkin’s lymphoma are excellent, but excess short-term and long-term morbidities from treatment remain a concern. Immunotherapy targeting both tumor antigens and the immunosuppressive tumor microenvironment in children, adolescents, and young adults with Hodgkin’s lymphoma may improve early response rates and eliminate toxic chemotherapy and radiation, thus minimizing toxicity. We conducted a phase II study to evaluate the safety and overall response rate of brentuximab vedotin and rituximab in combination with risk-adapted chemotherapy in children, adolescents, and young adults with newly diagnosed classic Hodgkin’s lymphoma (cHL). Methods This is a prospective, phase II, non-randomized, risk-assigned study. Patients were treated and evaluated between 2012 and 2020. Eligible patients were aged ≥1 and ≤30 years old with advanced stage, intermediate-risk, and high-risk newly diagnosed cHL. Patients received four or six cycles of brentuximab vedotin (1.2 mg/kg), doxorubicin (25 mg/m 2 ), vinblastine (6 mg/m 2 ), dacarbazine (375 mg/m 2 ), and rituximab (375 mg/m 2 ). Early response was evaluated following two cycles of therapy. Involved field radiotherapy (IFRT) was restricted to high-risk patients with both bulky disease and slow response or those not in complete response at the end of chemoimmunotherapy. Results Thirty patients were enrolled, with a median age of 15 years (4–23). There were 18 intermediate-risk and 12 high-risk patients. Toxicities included grade III mucositis (3%), infusion reaction (3%), and peripheral neuropathy (6%). There was a 100% complete response rate on completion of chemoimmunotherapy. Eighteen patients (60%) achieved a rapid early response. Four patients (13%) required IFRT. The 5-year event-free and overall survival rates were 100%, with a median follow-up of 62 months (18–105). Conclusions Immunotherapy with brentuximab vedotin, rituximab, and risk-adapted chemotherapy is safe in children, adolescents, and young adults with newly diagnosed cHL. We have demonstrated 100% complete response and 100% event-free and overall survival rates at a median 5-year follow-up, with a significant reduction in use of more toxic chemotherapy and IFRT. A larger cohort is required to confirm these preliminary findings. Trial registration number NCT02398240 .
PET Imaging of Dementia
Authors: Brian J. Burkett, Jeffrey C. Babcock, Val J. Lowe, Jonathan Graff-Radford, Rathan M. Subramaniam, Derek R. Johnson
Journal: Clinical Nuclear Medicine (2022)

PET imaging plays an essential role in achieving earlier and more specific diagnoses of dementia syndromes, important for clinical prognostication and optimal medical management. This has become especially vital with the recent development of pathology-specific disease-modifying therapy for Alzheimer disease, which will continue to evolve and require methods to select appropriate treatment candidates. Techniques that began as research tools such as amyloid and tau PET have now entered clinical use, making nuclear medicine physicians and radiologists essential members of the care team. This review discusses recent changes in the understanding of dementia and examines the roles of nuclear medicine imaging in clinical practice. Within this framework, multiple cases will be shown to illustrate a systematic approach of FDG PET interpretation and integration of PET imaging of specific molecular pathology including dopamine transporters, amyloid, and tau. The approach presented here incorporates contemporary understanding of both common and uncommon dementia syndromes, intended as an updated practical guide to assist with the sophisticated interpretation of nuclear medicine examinations in the context of this rapidly and continually developing area of imaging.
Reprogramming of Hepatic Metabolism and Microenvironment in Nonalcoholic Steatohepatitis
Authors: Liangyou Rui, Jiandie D. Lin
Journal: Annual Review of Nutrition (2022)

Nonalcoholic fatty liver disease (NAFLD), a spectrum of metabolic liver disease associated with obesity, ranges from relatively benign hepatic steatosis to nonalcoholic steatohepatitis (NASH). The latter is characterized by persistent liver injury, inflammation, and liver fibrosis, which collectively increase the risk for end-stage liver diseases such as cirrhosis and hepatocellular carcinoma. Recent work has shed new light on the pathophysiology of NAFLD/NASH, particularly the role of genetic, epigenetic, and dietary factors and metabolic dysfunctions in other tissues in driving excess hepatic fat accumulation and liver injury. In parallel, single-cell RNA sequencing studies have revealed unprecedented details of the molecular nature of liver cell heterogeneity, intrahepatic cross talk, and disease-associated reprogramming of the liver immune and stromal vascular microenvironment. This review covers the recent advances in these areas, the emerging concepts of NASH pathogenesis, and potential new therapeutic opportunities.
Omicron BA.1/1.1 SARS-CoV-2 Infection among Vaccinated Canadian Adults
Authors: Patrick E Brown, Sze Hang Fu, Aiyush Bansal, Leslie Newcombe, Karen Colwill, Geneviève Mailhot, Melanie Delgado-Brand, Anne-Claude Gingras, Arthur S Slutsky, Maria Pasic, Jeffrey Companion, Isaac I Bogoch, Ed Morawski, Teresa Lam, Angus Reid, Prabhat Jha
Journal: New England Journal of Medicine (2022)

C o r r e s p o n d e n c e Omicron BA.1/1.1 SARS-CoV-2 Infection among Vaccinated Canadian Adults To the Editor: The incidence of the omicron BA.1/1.1 variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which rapidly spread worldwide even among vaccinated persons, is incompletely defined. 1 We quantified the incidence of SARS-CoV-2 infection during the initial omicron BA.1/1.1 variant wave among Canadian adults 2 and the contribution of previous infection and concurrent vaccination to agespecific active immunity (Fig. S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). 3From May 2020 through March 2022, in the Action to Beat Coronavirus (Ab -C) study, we conducted four serial assessments of SARS-CoV-2 seropositivity, each involving 5000 to 9000 adults, using the Angus Reid Forum, a nationally representative online polling platform (Fig. S2).Driedblood-spot samples that had been obtained by the participants were tested with highly sensitive and specific chemiluminescence-based enzyme-linked immunosorbent assays targeting the spike protein, receptor-binding domain, and nucleocapsid (N) protein. 2,4Vaccines that have been used in Canada contain only spike protein and thus should not elicit N protein positivity. 5Approval for the study was obtained from the institutional review board at Unity Health Toronto.The 5031 adults who were surveyed in phase 4 of the Ab-C study and whose dried-blood-spot samples were received between January 24 and March 15, 2022, were broadly representative of Canadian adults.The study population had similar prevalences of obesity, smoking, diabetes, and vaccination against SARS-CoV-2 as the general Canadian adult population, but the study population included a lower percentage of lowereducated adults (Table S1).More women than men and more vaccinated adults than unvaccinated adults provided dried-blood-spot samples in phase 4 of the study.
Effect of awake craniotomy in glioblastoma in eloquent areas (GLIOMAP): a propensity score-matched analysis of an international, multicentre, cohort study
Authors: Jasper K W Gerritsen, Rosa H Zwarthoed, John L Kilgallon, Noah L Nawabi, Charissa A C Jessurun, Georges Versyck, Koen P Pruijn, Fleur L Fisher, Emma Larivière, Lien Solie, Rania A Mekary, Djaina D Satoer, Joost W Schouten, Eelke M Bos, Alfred Kloet, Rishi Nandoe Tewarie, Timothy R Smith, Clemens M F Dirven, Steven De Vleeschouwer, Marike L D Broekman, Arnaud J P E Vincent
Journal: The Lancet Oncology (2022)
Clarification of Conflict of Interest Disclosure
Authors: Sean C. Mackey
Journal: JAMA Internal Medicine (2022)

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Changes in US Clinician Waivers to Prescribe Buprenorphine Management for Opioid Use Disorder During the COVID-19 Pandemic and After Relaxation of Training Requirements
Authors: Joanne Spetz, Laurie Hailer, Caryl Gay, Matthew Tierney, Laura Schmidt, Bethany Phoenix, Susan Chapman
Journal: JAMA Network Open (2022)

This case series examines numbers of US clinicians receiving waivers from the Drug Enforcement Administration allowing them to prescribe buprenorphine for opioid use disorder before and during the COVID-19 pandemic.
Persisting uropathogenic Escherichia coli lineages show signatures of niche-specific within-host adaptation mediated by mobile genetic elements
Authors: Robert Thänert, JooHee Choi, Kimberly A. Reske, Tiffany Hink, Anna Thänert, Meghan A. Wallace, Bin Wang, Sondra Seiler, Candice Cass, Margaret H. Bost, Emily L. Struttmann, Zainab Hassan Iqbal, Steven R. Sax, Victoria J. Fraser, Arthur W. Baker, Katherine R. Foy, Brett Williams, Ben Xu, Pam Capocci-Tolomeo, Ebbing Lautenbach, Carey-Ann D. Burnham, Erik R. Dubberke, Jennie H. Kwon, Gautam Dantas
Journal: Cell Host & Microbe (2022)
Peak Troponin and CMR to Guide Management in Suspected ACS and Nonobstructive Coronary Arteries
Authors: Matthew G.L. Williams, Kate Liang, Estefania De Garate, Lucrezia Spagnoli, Emiliano Fiori, Amardeep Dastidar, Umberto Benedetto, Giovanni Biglino, Thomas W. Johnson, Thomas Luscher, Chiara Bucciarelli-Ducci
Journal: JACC. Cardiovascular imaging (2022)